Methylation in the Adult Mammalian Brain

Hongjun Song, Ph.D. Johns Hopkins University NIEHS Grant R21ES021957

Research funded in part by NIEHS reveals new information about an epigenetic mechanism that regulates gene expression in the mouse brain. This mechanism may contribute to the neurodevelopmental disorder Rett Syndrome and other neurological disorders.

Epigenetic changes, such as DNA methylation, control gene expression without changing DNA code. Historically, scientists believed methyl groups could only attach to a cytosine followed by a guanine, called CpG. But in recent years, they have been found on other sequences. In the new work, the researchers conducted a systematic analysis of DNA methylation in the adult mouse brain with single-base resolution and also mapped its genomic distribution.

The investigators found that adult mouse neurons have both non-CpG and CpG methylation. They observed non-CpG methylation in DNA regions without CpG methylation, meaning that it can likely control gene expression independently of CpG methylation. Additional experiments showed that non-CpG methylation occurs postnatally, is dynamic, and can repress gene expression. They also found that non-CpG methylation and CpG methylation are both read by the MeCP2 enzyme, which is important because MeCP2 mutations lead to problems in neural development and neuronal functions and are also linked to the neurodevelopmental disorder Rett syndrome.